ID   NRX2B_HUMAN             Reviewed;         666 AA.
AC   P58401;
DT   16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT   16-NOV-2001, sequence version 1.
DT   24-JAN-2024, entry version 161.
DE   RecName: Full=Neurexin-2-beta;
DE   AltName: Full=Neurexin II-beta;
DE   Flags: Precursor;
GN   Name=NRXN2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA   Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA   Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA   Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA   Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 90-666.
RA   Rowen L., Madan A., Qin S., Baradarani L., Birditt B., Bloom S., Burke J.,
RA   Dors M., Fleetwood P., Kaur A., Madan A., Nesbitt R., Pate D., Hood L.;
RT   "Sequencing of human neurexin II gene.";
RL   Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Neuronal cell surface protein that may be involved in cell
CC       recognition and cell adhesion.
CC   -!- SUBUNIT: Interacts (via cytoplasmic C-terminal region) with CASK (By
CC       similarity). Specific isoforms bind alpha-dystroglycan and neuroligins
CC       NLGN1, NLGN2 and NLGN3 (By similarity). Interacts with CBLN1, CBLN2
CC       and, less avidly, with CBLN4 (By similarity). Interacts with CLSTN3 (By
CC       similarity). {ECO:0000250|UniProtKB:E9Q7X7,
CC       ECO:0000250|UniProtKB:Q63376}.
CC   -!- SUBCELLULAR LOCATION: Presynaptic cell membrane {ECO:0000305}; Single-
CC       pass type I membrane protein {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC         Comment=A number of isoforms, alpha-type and beta-type are produced
CC         by alternative promoter usage. Beta-type isoforms differ from alpha-
CC         type isoforms in their N-terminus. Additional isoforms produced by
CC         alternative splicing seem to exist.;
CC       Name=1b;
CC         IsoId=P58401-1; Sequence=Displayed;
CC       Name=1a;
CC         IsoId=Q9P2S2-1; Sequence=External;
CC       Name=2a; Synonyms=Alpha-2B;
CC         IsoId=Q9P2S2-2; Sequence=External;
CC   -!- DOMAIN: Alternative splicing in the laminin G-like domain regulates
CC       binding to alpha-dystroglycan.
CC   -!- PTM: O-glycosylated; contains heparan sulfate. Heparan sulfate
CC       attachment is required for synapse development by mediating
CC       interactions with neuroligins. {ECO:0000250|UniProtKB:E9PUN2}.
CC   -!- SIMILARITY: Belongs to the neurexin family. {ECO:0000305}.
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DR   EMBL; AP001092; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC044790; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS8078.1; -. [P58401-1]
DR   RefSeq; NP_620063.1; NM_138734.2. [P58401-1]
DR   PDB; 4NXR; X-ray; 1.90 A; B=659-666.
DR   PDBsum; 4NXR; -.
DR   AlphaFoldDB; P58401; -.
DR   SMR; P58401; -.
DR   BioGRID; 114780; 6.
DR   IntAct; P58401; 1.
DR   MINT; P58401; -.
DR   GlyCosmos; P58401; 1 site, No reported glycans.
DR   BioMuta; NRXN2; -.
DR   DMDM; 17368287; -.
DR   MassIVE; P58401; -.
DR   PeptideAtlas; P58401; -.
DR   ProteomicsDB; 57072; -. [P58401-1]
DR   TopDownProteomics; P58401-1; -. [P58401-1]
DR   Antibodypedia; 63686; 62 antibodies from 7 providers.
DR   DNASU; 9379; -.
DR   Ensembl; ENST00000301894.6; ENSP00000301894.2; ENSG00000110076.21. [P58401-1]
DR   GeneID; 9379; -.
DR   UCSC; uc001oap.3; human. [P58401-1]
DR   AGR; HGNC:8009; -.
DR   CTD; 9379; -.
DR   DisGeNET; 9379; -.
DR   GeneCards; NRXN2; -.
DR   HGNC; HGNC:8009; NRXN2.
DR   HPA; ENSG00000110076; Tissue enriched (brain).
DR   MIM; 600566; gene.
DR   neXtProt; NX_P58401; -.
DR   OpenTargets; ENSG00000110076; -.
DR   PharmGKB; PA31787; -.
DR   VEuPathDB; HostDB:ENSG00000110076; -.
DR   GeneTree; ENSGT00940000155978; -.
DR   HOGENOM; CLU_025785_2_0_1; -.
DR   OrthoDB; 2999458at2759; -.
DR   PathwayCommons; P58401; -.
DR   Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR   SignaLink; P58401; -.
DR   SIGNOR; P58401; -.
DR   BioGRID-ORCS; 9379; 16 hits in 1149 CRISPR screens.
DR   ChiTaRS; NRXN2; human.
DR   GeneWiki; NRXN2; -.
DR   GenomeRNAi; 9379; -.
DR   Pharos; P58401; Tbio.
DR   Proteomes; UP000005640; Chromosome 11.
DR   Bgee; ENSG00000110076; Expressed in right hemisphere of cerebellum and 139 other cell types or tissues.
DR   ExpressionAtlas; P58401; baseline and differential.
DR   GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0050839; F:cell adhesion molecule binding; TAS:BHF-UCL.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0097109; F:neuroligin family protein binding; TAS:BHF-UCL.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:BHF-UCL.
DR   GO; GO:0007158; P:neuron cell-cell adhesion; TAS:BHF-UCL.
DR   GO; GO:0007165; P:signal transduction; NAS:BHF-UCL.
DR   CDD; cd00110; LamG; 1.
DR   Gene3D; 2.60.120.200; -; 1.
DR   InterPro; IPR013320; ConA-like_dom_sf.
DR   InterPro; IPR001791; Laminin_G.
DR   InterPro; IPR003585; Neurexin-like.
DR   PANTHER; PTHR15036:SF52; NEUREXIN-2; 1.
DR   PANTHER; PTHR15036; PIKACHURIN-LIKE PROTEIN; 1.
DR   Pfam; PF02210; Laminin_G_2; 1.
DR   SMART; SM00294; 4.1m; 1.
DR   SMART; SM00282; LamG; 1.
DR   SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1.
DR   PROSITE; PS50025; LAM_G_DOMAIN; 1.
DR   Genevisible; P58401; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative promoter usage; Alternative splicing; Calcium;
KW   Cell adhesion; Cell membrane; Cell projection; Glycoprotein;
KW   Heparan sulfate; Membrane; Metal-binding; Proteoglycan; Reference proteome;
KW   Repeat; Signal; Synapse; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..50
FT                   /evidence="ECO:0000250|UniProtKB:Q63376"
FT   CHAIN           51..666
FT                   /note="Neurexin-2-beta"
FT                   /id="PRO_0000019497"
FT   TOPO_DOM        51..590
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        591..611
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        612..666
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          91..299
FT                   /note="Laminin G-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT   REGION          1..30
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          327..346
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          412..443
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          479..580
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          633..666
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        529..555
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        650..666
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         143
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:Q63373"
FT   BINDING         160
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:Q63373"
FT   BINDING         242
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:Q63373"
FT   BINDING         244
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:Q63373"
FT   CARBOHYD        190
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        354
FT                   /note="O-linked (Xyl...) (heparan sulfate) serine"
FT                   /evidence="ECO:0000250|UniProtKB:E9PUN2"
FT   STRAND          660..665
FT                   /evidence="ECO:0007829|PDB:4NXR"
SQ   SEQUENCE   666 AA;  70927 MW;  FD0B2FD353F63C6C CRC64;
     MPPGGSGPGG CPRRPPALAG PLPPPPPPPP PPLLPLLPLL LLLLLGAAEG ARVSSSLSTT
     HHVHHFHSKH GTVPIAINRM PFLTRGGHAG TTYIFGKGGA LITYTWPPND RPSTRMDRLA
     VGFSTHQRSA VLVRVDSASG LGDYLQLHID QGTVGVIFNV GTDDITIDEP NAIVSDGKYH
     VVRFTRSGGN ATLQVDSWPV NERYPAGNFD NERLAIARQR IPYRLGRVVD EWLLDKGRQL
     TIFNSQAAIK IGGRDQGRPF QGQVSGLYYN GLKVLALAAE SDPNVRTEGH LRLVGEGPSV
     LLSAETTATT LLADMATTIM ETTTTMATTT TRRGRSPTLR DSTTQNTDDL LVASAECPSD
     DEDLEECEPS TGGELILPII TEDSLDPPPV ATRSPFVPPP PTFYPFLTGV GATQDTLPPP
     AARRPPSGGP CQAERDDSDC EEPIEASGFA SGEVFDSSLP PTDDEDFYTT FPLVTDRTTL
     LSPRKPAPRP NLRTDGATGA PGVLFAPSAP APNLPAGKMN HRDPLQPLLE NPPLGPGAPT
     SFEPRRPPPL RPGVTSAPGF PHLPTANPTG PGERGPPGAV EVIRESSSTT GMVVGIVAAA
     ALCILILLYA MYKYRNRDEG SYQVDQSRNY ISNSAQSNGA VVKEKAPAAP KTPSKAKKNK
     DKEYYV
//